| 1. |
- Tirkkonen, M, et al.
(författare)
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Distinct somatic genetic changes associated with tumor progression in carriers of BRCA1 and BRCA2 germ-line mutations
- 1997
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Ingår i: Cancer Research. - 0008-5472. ; 57:7, s. 7-1222
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Tidskriftsartikel (refereegranskat)abstract
- BRCA1 and BRCA2 mutations confer increased risk for development of breast cancer, but a number of additional, currently largely unknown, somatic genetic defects must also accumulate in the breast epithelial cells before malignancy develops. To evaluate the nature of these additional somatic genetic defects, we performed a genome-wide survey by comparative genomic hybridization on breast cancers from 21 BRCA1 mutation carriers, 15 BRCA2 mutation carriers, and 55 unselected controls. The total number of genetic changes was almost two times higher in tumors from both BRCA1 and BRCA2 mutation carriers than in the control group. In BRCA1 tumors, losses of 5q (86%), 4q (81%), 4p (64%), 2q (40%), and 12q (40%) were significantly more common than in the control group (7-13%). BRCA2 tumors were characterized by a higher frequency of 13q (73%) and 6q (60%) losses and gains of 17q22-q24 (87%) and 20q13 (60%) as compared to the prevalence of these changes in the control group (12-18%). In conclusion, accumulation of somatic genetic changes during tumor progression may follow a unique pathway in individuals genetically predisposed to cancer, especially by the BRCA1 gene. Activation or loss of genes in the affected chromosomal regions may be selected for during tumor progression in cells lacking functional BRCA1 or BRCA2. Identification of such genes could provide targets for therapeutic intervention and early diagnosis.
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| 2. |
- Tirkkonen, M, et al.
(författare)
-
Somatic genetic alterations in BRCA2-associated and sporadic male breast cancer
- 1999
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Ingår i: Genes, Chromosomes and Cancer. - 1045-2257. ; 24:1, s. 56-61
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Tidskriftsartikel (refereegranskat)abstract
- The genetic changes underlying the development and progression of male breast cancer are poorly understood. Germline BRCA2 mutations account for a significant part of male breast cancer, but the majority of patients lack a known inherited predisposition. We recently demonstrated that the progression of breast cancer in female carriers of a germline BRCA1 or BRCA2 mutation follows specific genetic pathways, distinct from each other and from sporadic breast cancer. In the present study, we performed a genome-wide survey by comparative genomic hybridization (CGH) of somatic genetic aberrations in 26 male breast cancers, including five tumors from BRCA2 mutation carriers. BRCA2 tumors exhibited a significantly higher number of chromosomal aberrations than sporadic tumors. The most common alterations in sporadic male breast cancer were +1q (38%), +8q (33%), +17q (33%), -13q (29%), and -8p (24%). In tumors from BRCA2 mutation carriers, the five most common genetic changes were +8q (100%), +20q (100%), +17q (80%), -13q (80%), and -6q (60%). The CGH results in these two groups of male breast cancers are almost identical to those identified in the corresponding sporadic and BRCA2-associated female breast cancers. The results suggest that despite substantial hormonal differences between females and males, similar genetic changes are selected for during tumor progression. Furthermore, the presence of a highly penetrant germline BRCA2 mutation apparently leads to a characteristic somatic tumor progression pathway, again shared between affected male and female mutation carriers.
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